CAPN10 mRNA splicing and decay is not affected by a SNP associated with susceptibility to type 2 diabetes

The mRNA concentration of CAPN10, a T2D susceptibility gene was measured in white blood cells of T2D and healthy subjects, as well as the transcript half-life in two SNP-43 genotyped human cell lines, to evaluate a possible relationship between this SNP-43 and the transcript half-life. T2D patients with the SNP-43 G-allele had 4.6-fold more CAPN10 transcripts compared to subjects with the A-allele. The mRNA half-life of this transcript in 293T cells (SNP-43 G/G) and Jurkat cells (SNP-43 A/A) was of 8 h. We provide evidence that in T2D subjects the G-allele increases the CAPN10 mRNA levels. We propose a defective CAPN10 pre-mRNA processing is responsible for the decreased levels of SNP-43 A-allele transcripts in peripheral white cells of healthy and T2D individuals.